Proenkephalin gene regulation in the paraventricular nucleus by GABA: interactions with opioid systems in a transgenic model
| Autor: | David Borsook, Olga Smirnova, Olga Falkowski |
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| Rok vydání: | 1998 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Transgene Narcotic Antagonists Recombinant Fusion Proteins Hypothalamus Mice Transgenic Biology Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Organ Culture Techniques Stress Physiological Internal medicine medicine Animals Humans GABA-A Receptor Agonists Protein Precursors Opioid peptide Cells Cultured gamma-Aminobutyric Acid Saline Solution Hypertonic Muscimol Aminooxyacetic Acid Enkephalins beta-Galactosidase Aminooxyacetic acid Naltrexone Proenkephalin Endocrinology Baclofen nervous system chemistry Gene Expression Regulation Paraventricular Hypothalamic Nucleus |
| Zdroj: | Journal of neurochemistry. 70(2) |
| ISSN: | 0022-3042 |
| Popis: | GABA, which is present at high levels within the paraventricular nucleus (PVN) of the hypothalamus, has been implicated in neuroendocrine regulation. Here we use a transgenic mouse model expressing a human proenkephalin-beta-galactosidase fusion gene, in which both up-regulation and down-regulation of gene expression can be measured easily, to study the effects of GABA on basal and stress-induced gene expression within the PVN. This model has been shown previously to be appropriately physiologically regulated by stress within the PVN. Acute systemic administration of GABA, of aminooxyacetic acid, and of the selective GABA(B) receptor agonist, baclofen, induces transgene expression in the PVN. Chronic administration of aminooxyacetic acid inhibits both basal and stress-induced transgene expression. Acute or chronic administration of the selective GABA(A) agonist, muscimol, inhibits both basal and stress-induced expression of the transgene. Muscimol also inhibits transgene expression in hypothalamic slice cultures in which extrahypothalamic afferents are removed. It is surprising that, following chronic aminooxyacetic acid administration, the opiate antagonist naltrexone induces transgene expression in a manner similar to that observed with naloxone-precipitated opioid withdrawal and that expression is accompanied by a behavioral syndrome that partially mimicks opioid withdrawal. Taken together with our previous work, and using gene expression as our read-out, we conclude that transgene-expressing PVN neurons receive tonic inhibitory inputs mediated via GABA(A) receptors. Moreover, these inhibitory inputs can themselves be inhibited via GABA(B) and mu-opioid receptors. |
| Databáze: | OpenAIRE |
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